rs200225698

chrX-74745579-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001008537.3(NEXMIF):c.72A>G(p.Lys24=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000305 in 1,182,252 control chromosomes in the GnomAD database, including 1 homozygotes. There are 124 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00034 (1 hom., 13 hem., cov: 22)
  • Exomes 𝑓: 0.00030 (0 hom. 111 hem.)
• Consequence: NEXMIF NM_001008537.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.664

Genes affected

NEXMIF (HGNC:29433): (neurite extension and migration factor) An inversion on the X chromosome which disrupts this gene and a G-protein coupled purinergic receptor gene located in the pseudoautosomal region of the X chromosome has been linked to X linked cognitive disability.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant X-74745579-T-C is Benign according to our data. Variant chrX-74745579-T-C is described in ClinVar as [Benign]. Clinvar id is 474075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.664 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEXMIF	NM_001008537.3	c.72A>G	p.Lys24=	synonymous_variant	2/4	ENST00000055682.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEXMIF	ENST00000055682.12	c.72A>G	p.Lys24=	synonymous_variant	2/4	1	NM_001008537.3	P1
NEXMIF	ENST00000616200.2	c.72A>G	p.Lys24=	synonymous_variant	2/5	1		P1
NEXMIF	ENST00000642681.2	c.72A>G	p.Lys24=	synonymous_variant	2/3

Frequencies

GnomAD3 genomes AF: 0.000340 AC: 38 AN: 111731 Hom.: 1 Cov.: 22 AF XY: 0.000384 AC XY: 13 AN XY: 33891

Gnomad AFR AF: 0.0000976

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00152

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000301

Gnomad OTH AF: 0.00200

GnomAD3 exomes AF: 0.000460 AC: 84 AN: 182662 Hom.: 0 AF XY: 0.000461 AC XY: 31 AN XY: 67306

Gnomad AFR exome AF: 0.0000762

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000418

Gnomad OTH exome AF: 0.00178

GnomAD4 exome AF: 0.000302 AC: 323 AN: 1070466 Hom.: 0 Cov.: 25 AF XY: 0.000326 AC XY: 111 AN XY: 340850

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00162

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000296

Gnomad4 OTH exome AF: 0.000532

GnomAD4 genome AF: 0.000340 AC: 38 AN: 111786 Hom.: 1 Cov.: 22 AF XY: 0.000383 AC XY: 13 AN XY: 33956

Gnomad4 AFR AF: 0.0000974

Gnomad4 AMR AF: 0.00152

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000301

Gnomad4 OTH AF: 0.00197

Alfa AF: 0.000434 Hom.: 4

Bravo AF: 0.000582

EpiCase AF: 0.000492

EpiControl AF: 0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 22, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	7.9
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200225698; hg19: chrX-73965414;